Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin (< 500 μm) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV (eFOV) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV-microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV-microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV-microendoscopes are, therefore, small-crosssection ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.
|Original language||English (US)|
|State||Published - Oct 13 2020|
Bibliographical noteKAUST Repository Item: Exported on 2020-10-15
Acknowledged KAUST grant number(s): BAS/1/1064-01-01
Acknowledgements: We thank M. Dal Maschio for discussion at an initial stage of the project, F. Nespoli for preliminary analysis, and B. Sabatini and A. Begue for critical reading an early version of this manuscript. We thank D.S. Kim and the GENIE project for the constructs Addgene viral prep # 100845-AAV1 and #104492-AAV1, H. Zeng for the construct Addgene viral prep # 51502-AAV1, and J.M. Wilson for the construct Addgene viral prep # 105558-AAV1. This work was supported by an IIT interdisciplinary grant and in part by ERC (NEURO-PATTERNS), NIH Brain Initiative (U01 NS090576, U19 NS107464, R01NS109961), FP7 (DESIRE), MIUR FIRB (RBAP11X42L), and Flag-Era JTC Human Brain Project (SLOW-DYN). CL acknowledges support from KAUST under baseline funding BAS/1/1064-01-01.